Northwestern UniversityDownload PDFPatent Trials and Appeals BoardMay 4, 20202019004750 (P.T.A.B. May. 4, 2020) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 13/772,796 02/21/2013 Thomas W. McDade 702581.00478.NU2012-004 6018 69220 7590 05/04/2020 Quarles & Brady LLP (Northwestern) Attn: IP Docket 411 East Wisconsin Ave Milwaukee, WI 53202-4426 EXAMINER MARCSISIN, ELLEN JEAN ART UNIT PAPER NUMBER 1641 NOTIFICATION DATE DELIVERY MODE 05/04/2020 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): pat-dept@quarles.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte THOMAS W. MCDADE, WILLIAM E. FUNK, and DAVID B. SEIFER ____________ Appeal 2019-004750 Application 13/772,796 Technology Center 1600 ____________ Before FRANCISCO C. PRATS, RACHEL H. TOWNSEND, and CYNTHIA M. HARDMAN, Administrative Patent Judges. PRATS, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject claims 40–59. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant states that the “the real party in interest is Northwestern University, by assignment from the inventors recorded in the U.S. Patent and Trademark Office on March 7, 2013, at Reel 029940, Frame 0787.” Appeal Br. 1. Appeal 2019-004750 Application 13/772,796 2 STATEMENT OF THE CASE The following rejections are before us for review: (1) Claims 40, 41, and 46, under pre-AIA 35 U.S.C. § 102(b) as anticipated by INSERM2 (Ans. 3–4); (2) Claims 56, 58, and 59, under 35 U.S.C. § 103(a) as unpatentable over INSERM and McDade3 (Ans. 4–7); (3) Claims 40–46, 49, 50, and 54, under 35 U.S.C. § 103(a) as unpatentable over Place4 and INSERM (Ans. 7–14); (4) Claims 40–50 and 54–59, under 35 U.S.C. § 103(a) as unpatentable over Place, INSERM, and McDade (Ans. 14–21); and (5) Claims 51–53, under 35 U.S.C. § 103(a) as unpatentable over Place, INSERM, McDade, and Mohammed5 (Ans. 21–22). Independent claims 40 and 56 are representative and read as follows: 40. A method comprising: a) contacting a whole blood sample from a finger stick of a subject directly with labeled antibodies specific for Anti-Mullerian hormone (labelled anti- AMH antibodies) under conditions whereby an aggregate is formed comprising the labelled anti- AMH antibodies and AMH in the whole blood sample, wherein the labelled anti-AMH antibodies are labeled with nanoparticles that generate a colorimetric or fluorescent signal when the aggregate is formed and the colorimetric or fluorescent signal has an intensity that is 2 EP 2 161 579 A1 (published Aug. 26, 2008). 3 Thomas W. McDade et al., What a Drop Can Do: Dried Blood Spots as a Minimally Invasive Method for Integrating Biomarker in Population-Based Research, 44 DEMOGRAPHY 899–925 (2007). 4 US 2009/0275060 A1 (published Nov. 5, 2009). 5 US 2008/0254441 A1 (published Oct. 16, 2008). Appeal 2019-004750 Application 13/772,796 3 proportional to concentration of AMH in the whole blood sample; and b) detecting the intensity of the signal. 56. A method comprising: a) obtaining a whole blood sample from a finger stick of a subject; b) contacting the whole blood sample from the finger stick of the subject directly with labeled antibodies specific for Anti-Mullerian hormone (labelled anti- AMH antibodies) under conditions whereby an aggregate is formed comprising the labelled anti- AMH antibodies and AMH in the whole blood sample, wherein the labelled anti-AMH antibodies are labeled with nanoparticles that generate a colorimetric or fluorescent signal when the aggregate is formed and the colorimetric or fluorescent signal has an intensity that is proportional to concentration of AMH in the whole blood sample; and c) detecting the intensity of the signal. Appeal Br. 23, 26 (emphasis added to limitation primarily at issue). ANTICIPATION The Examiner’s Rejection In rejecting claims 40, 41, and 46 as anticipated by INSERM, the Examiner determined that INSERM described a process for detecting Anti- Mullerian hormone (AMH). Ans. 3. The Examiner found that INSERM’s process included directly contacting a whole blood sample with labeled antibodies encompassed by the claims, thereby forming an aggregate, and then detecting the intensity of the signal of the labeled antibodies. Id. at 3–4. The Examiner determined, as to the limitation “contacting a whole blood sample from a finger stick of a subject,” that independent claim 40 Appeal 2019-004750 Application 13/772,796 4 “does not actually include/recite a step of obtaining a finger stick blood sample. This recitation is a product-by-process limitation, defining the manner in which the whole blood sample is obtained.” Ans. 4. The Examiner determined that the “process by which the whole blood sample is obtained does not clearly impart any structural differen[ce] in this case to the resultant whole blood sample,” and “[a]s no clear limitations are apparent as a result of this product by process limitation, it is Appellant’s burden to establish an unobvious difference between the claimed invention and the cited art. See MPEP 2113.” Ans. 4. Specifically, the Examiner reasoned, “it is the case that a whole blood sample as recited by INSERM is the same as a whole blood sample presently claimed (whether obtained by a finger stick or by another means, the whole blood sample is expected to be the same)[;] as such, INSERM anticipates the claim.” Ans. 4. Analysis As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992): [T]he examiner bears the initial burden . . . of presenting a prima facie case of unpatentability. . . . After evidence or argument is submitted by the applicant in response, patentability is determined on the totality of the record, by a preponderance of evidence with due consideration to persuasiveness of argument. Having carefully considered the arguments and evidence advanced by Appellant and the Examiner, Appellant persuades us that the preponderance of the evidence does not support the Examiner’s determination that INSERM describes a process having all of the steps and features required by rejected claims 40, 41, and 46. In particular, we agree with Appellant that the Examiner has not shown sufficiently that INSERM describes contacting Appeal 2019-004750 Application 13/772,796 5 a whole blood sample “from a finger stick of a subject” directly with labeled anti-AMH antibodies, as recited in Appellant’s independent claim 40. Appeal Br. 23. INSERM describes a method for “quantifying the presence of at least one biologically active form of Anti-Müllerian Hormone (AMH) in a sample, said method comprising detecting the presence of cleaved AMH or C-terminal AMH in said sample.” INSERM ¶ 39 (emphasis added). INSERM discloses that, in one embodiment, “quantification of at least one of the biologically active forms of AMH in a sample may be achieved by a competitive immunoassay. Example[s] of competitive immunoassays include . . . fluorescent immunoassay[s].” INSERM ¶ 54 (emphasis added). INSERM discloses that “the sample susceptible to contain biological active forms of AMH is a biological sample, such as cell lysates or culture medium, or is a body fluid such as whole blood, serum, plasma, follicular fluid, seminal fluid, synovial fluid, cerebrospinal fluid, saliva, or urine.” INSERM ¶ 48 (emphasis added). INSERM discloses that, “[i]n a preferred embodiment, said sample is a serum sample, a whole blood sample, a plasma sample, a follicular fluid sample, a seminal fluid sample.” INSERM ¶ 49 (emphasis added). As noted above, the Examiner determined that INSERM’s disclosure of quantifying AMH in a whole blood sample necessarily, that is inherently, describes using a sample from a finger stick of a subject, as recited in Appellant’s claim 40, because a whole blood sample from a finger stick is indistinguishable from other types of whole blood samples. See Ans. 4. We are not persuaded. A number of references cited by Appellant support Appellant’s contention that the composition of a whole blood Appeal 2019-004750 Application 13/772,796 6 sample from a finger stick is not necessarily the same as the composition of other types of whole blood samples, e.g., as obtained from venipuncture. See Kupke 19816 (disclosing that “concentrations of various clinical- chemical substances in the capillary and venous blood serum of apparently healthy adults (20–30 yr) were examined in the fasting state” and that “[t]otal protein, bilirubin, calcium, sodium and chloride concentrations were significantly lower (≤ 5%) in capillary than in venous serum”); see also Larsson-Cohn7 (disclosing that simultaneous measurement of capillary and venous blood glucose concentrations during oral glucose tolerance tests produced significantly different results in samples taken after 15–90 minutes “indicat[ing] that the verdict [as to ‘normal’ or ‘abnormal’] will in some cases be influenced by the route by which the blood was obtained”); see also Moe8 (disclosing comparison of hemoglobin, hematocrit, and red blood cell evaluations in capillary (“skin-prick”) and venous blood in 30 adults and 30 children and finding that “[h]igher mean values were found in venous blood, particularly in the children”). It is undisputed on this record that INSERM does not expressly describe using a whole blood sample from a finger stick of a subject as the sample in which AMH is detected. Because the composition of a blood 6 I.R. Kupke, On the composition of capillary and venous blood serum, 112 CLIN. CHIM. ACTA 177–185 (1981) (abstract only). 7 U. Larsson-Cohn, Differences between Capillary and Venous Blood Glucose during Oral Glucose Tolerance Tests, 36 SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION 805–808 (1976) (abstract only). 8 P.J. Moe, Hemoglobin, Hematocrit and Red Blood Cell Count in “Capillary (Skin-Prick) Blood Compared to Venous Blood In Children, 59 ACTA PAEDIATRICA 49–51 (1970) (abstract only). Appeal 2019-004750 Application 13/772,796 7 sample can vary depending on whether the sample is venous blood, as opposed to blood obtained from a finger stick (see, e.g., Kupke 1981; Larsson-Cohn; Moe), we are not persuaded by the Examiner’s product-by- process rationale, and thus find insufficient support for the Examiner’s finding that INSERM’s generic disclosure of using a whole blood sample (see INSERM ¶¶ 48, 49) inherently describes using a whole blood sample from a finger stick of a subject, as recited in Appellant’s claim 40. We therefore agree with Appellant that INSERM does not anticipate independent claim 40, or its dependent claims 41, 46. The Examiner contends that Kupke 1981, Larsson-Cohn, and Moe do not show that INSERM does not anticipate claim 40, because the differences between venous and skin prick blood as to the analytes evaluated in those references do not establish that AMH would be undetectable in a whole blood sample from a finger stick of a subject. See Ans. 29–30. We are not persuaded. It is well settled that, “[t]o anticipate a claim, a prior art reference must disclose every limitation of the claimed invention, either explicitly or inherently.” In re Schreiber, 128 F.3d 1473, 1477 (Fed. Cir. 1997). In the present case, Appellant’s claim 40 requires the sample in the claimed process to be “a whole blood sample from a finger stick of a subject.” Appeal Br. 23. Thus, the issue as to this anticipation rejection is not, as the Examiner contends, whether a skilled artisan would have expected INSERM’s whole blood sample to contain an assayable amount of AMH. Rather, the issue as to the Examiner’s anticipation rejection is whether the whole blood sample described in INSERM is the same as the Appeal 2019-004750 Application 13/772,796 8 whole blood sample from a finger stick of a subject, recited in Appellant’s claim 40. It is undisputed that INSERM does not explicitly disclose using a whole blood sample from a finger stick in its process. For INSERM to inherently describe using a whole blood sample from a finger stick in its process, it must be unavoidable that INSERM’s sample is the same as a whole blood sample from a finger stick. See Agilent Technologies, Inc. v. Affymetrix, Inc., 567 F.3d 1366, 1383 (Fed. Cir. 2009) (“The very essence of inherency is that one of ordinary skill in the art would recognize that a reference unavoidably teaches the property in question.”) (emphasis added). In the present case, as discussed above, Appellant has advanced evidence that the composition of a whole blood sample differs significantly depending on whether the sample is from a finger stick, or is a venous blood sample. We are not persuaded, therefore, that in describing the use of a “whole blood sample” (INSERM ¶ 49), INSERM unavoidably, i.e. inherently, describes a sample that is compositionally identical to the whole blood sample from a finger stick recited in Appellant’s claim 40. In sum, for the reasons discussed, Appellant persuades us that the Examiner has not shown by a preponderance of the evidence that INSERM describes a process that has all of the steps and features required by Appellant’s claim 40. We therefore reverse the Examiner’s rejection of claim 40, and its dependent claims 41 and 46, as anticipated by INSERM. OBVIOUSNESS—INSERM AND MCDADE The Examiner’s Rejection In rejecting claims 56, 58, and 59 for obviousness over INSERM and McDade, the Examiner found that INSERM described a process with nearly Appeal 2019-004750 Application 13/772,796 9 all of the steps and features recited in the claims, but conceded that INSERM differs from the claims in that “INSERM fails to teach a step of obtaining the whole blood sample from a finger stick of a subject.” Ans. 5. As evidence that Appellant’s claimed process would have been obvious despite the difference between INSERM and the claimed process, the Examiner cited McDade as disclosing that, when determining the concentration of analytes in blood, whole dried blood samples obtained by a finger stick had a number of advantages over samples obtained through venipuncture. See Ans. 5–6. Based on the advantages taught in McDade, the Examiner reasoned that a skilled artisan would have considered it obvious to modify INSERM’s method “to first perform a step obtaining the whole blood sample from a finger stick, as taught by McDade et al., when performing methods for detection of AMH using whole blood samples as taught by INSERM.” Ans. 6. In particular, the Examiner reasoned that “acquiring such blood samples is minimally invasive, convenient regarding collection (don’t need medically trained staff, can be performed in home or by participant themselves), low cost (compared to venipuncture), and allows access to physiological information that would otherwise be unattainable in a nonclinical setting (McDade et al.).” Ans. 6. Analysis We select claim 56 as representative of the claims subject to this rejection. See 37 C.F.R. § 41.37(c)(1)(iv). Having carefully considered the arguments and evidence advanced by Appellant and the Examiner, Appeal 2019-004750 Application 13/772,796 10 Appellant does not persuade us that the preponderance of the evidence fails to support the Examiner’s conclusion of obviousness as to claim 56. Appellant contends it has “provided ample evidence that whole blood obtained from a finger stick from a subject would not be recognized in the art as being suitable for directly detecting circulating anti-Mullerian hormone (AMH) in the subject.” Appeal Br. 16 (citing McDade Declaration,9 Kelso Declaration,10 Fleming11). We are not persuaded. As noted above, INSERM discloses “quantification of at least one of the biologically active forms of AMH in a sample may be achieved by a competitive immunoassay. Example[s] of competitive immunoassays include . . . fluorescent immunoassay[s].” INSERM ¶ 54 (emphasis added). As also noted above, INSERM discloses that, “[i]n a preferred embodiment, said sample is a serum sample, a whole blood sample, a plasma sample, a follicular fluid sample, a seminal fluid sample.” INSERM ¶ 49 (emphasis added). Given INSERM’s express disclosure that its sample in a preferred embodiment is a whole blood sample, we are not persuaded by Appellant’s contentions that INSERM does not teach or suggest directly contacting a whole blood sample with a fluorescently labeled anti-AMH antibody. In particular, given INSERM’s teaching that any of serum, plasma, or whole blood are useful samples in its preferred embodiment (INSERM ¶ 49), we are not persuaded that a skilled artisan would have interpreted INSERM’s 9 Declaration of Thomas W. McDade, Ph.D. (signed Oct. 21, 2014). 10 Declaration of David M. Kelso, Ph.D. (signed Sept. 25, 2015). 11 Richard Fleming et al., Stability of AMH measurement in blood and avoidance of proteolytic changes, 26 REPRODUCTIVE BIOMEDICINE ONLINE 130–132 (2013). Appeal 2019-004750 Application 13/772,796 11 disclosure of a whole blood sample as equating to a teaching that antibody- based quantitation of AMH required serum or plasma separation from the whole blood. See Appeal Br. 8–10. And, contrary to Appellant’s contentions that skilled artisans would have considered whole blood from a finger stick an unsuitable sample for direct antibody-based quantitation of circulating AMH in a subject, the McDade reference discloses that a dried whole blood sample from a finger stick provides a sufficient amount of material for quantifying many analytes of interest. See McDade 906 (“In most cases, an analyte that can be measured in serum or plasma can also be assayed in DBS [dried blood spot] samples.”); see also id. (“The relatively recent development of highly sensitive and specific immunoassays has facilitated analysis of biomarkers in small, microliter quantities of blood, but there are limits.”). McDade explains further: A typical drop of blood will contain approximately 50 μL of whole blood and will result in a DBS sample approximately 12 mm in diameter. Such a spot will yield seven 3.2-mm discs of blood. A full card of five blood spots will, therefore, contain enough sample to analyze 35 analytes requiring one 3.2-mm disc, or 17 analytes requiring two such discs. McDade 907. We acknowledge the McDade reference’s disclosure that not all analytes are amenable to quantitation from a DBS. See, e.g., McDade 906 (“[T]here are limits.”); id. at 907 (“In some cases, quantifying an analyte of interest in DBS samples may not be possible.”). As our reviewing court has explained, however, “[o]bviousness does not require absolute predictability of success. . . . For obviousness under § 103, all that is required is a reasonable expectation of success.” In re Appeal 2019-004750 Application 13/772,796 12 Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009) (quoting In re O’Farrell, 853 F.2d 894, 903–04 (Fed. Cir. 1988) (emphasis removed). Given the disclosures in the McDade reference, noted above, that a dried whole blood sample from a finger stick provides a sufficient amount of material for quantifying many analytes of interest by immunoassay, we agree with the Examiner that a skilled artisan would have had a reasonable expectation of success in using McDade’s whole blood finger stick sample as the whole blood sample in INSERM’s antibody-based AMH quantitation process. We acknowledge the statements in the McDade Declaration that the state of the art was that skilled artisans would not have expected whole blood to be useful for accurate determination of AMH levels: Prior to our determining that whole blood could be used to accurately detect levels of AMH, it would have been unexpected that whole blood could be used to accurately detect levels of AMH. Rather, endocrinologists would have expected that a serum sample obtained via a venipuncture blood draw would need to be used in order to accurately detect levels of AMH (i.e., the current gold-standard serum-based assay method). This is at least partially because whole blood, in comparison to serum, is more complex and contains components that can potentially interfere with accurately determining AMH levels. McDade Decl. ¶ 7. We also acknowledge the similar statement in the Kelso Declaration that “only a serum sample obtained via a venipuncture blood draw would have been viewed as a suitable sample for accurately determining concentration of AMH.” Kelso Decl. ¶ 6. It is well settled, however, that to be persuasive of nonobviousness, an expert’s opinion must be supported by objective evidence. See Ashland Oil, Appeal 2019-004750 Application 13/772,796 13 Inc. v. Delta Resins & Refractories, Inc., 776 F.2d 281, 294 (Fed. Cir. 1985) (“Lack of factual support for expert opinion going to factual determinations . . . may render the testimony of little probative value in a validity determination.”) (citing In re Altenpohl, 500 F.2d 1151, 1158 (CCPA 1974)). In the present case, neither the McDade Declaration nor the Kelso Declaration provides any specific objective evidence supporting the statements that the state of the art was that a dried whole blood sample from a finger stick, as taught in the McDade reference, would have been unsuitable for antibody-based AMH quantification methods, as taught in INSERM. Indeed, neither the McDade Declaration nor the Kelso Declaration directly addresses the teachings in the McDade reference discussed above, nor do those declarations explain specifically why the McDade reference’s teachings would have failed to provide a skilled artisan with a reasonable expectation of successfully using a whole blood finger stick sample as the whole blood sample in INSERM’s antibody-based AMH quantitation process. We acknowledge the McDade Declaration’s statement that whole blood contains components that can interfere with accurate AMH determination. McDade Decl. ¶ 7. The McDade reference, however, while recognizing potential interference from cellular components in a whole blood sample from a finger stick, nonetheless states that “[t]his is not a common problem, although the presence of lysed red blood cells has proven to be an insurmountable obstacle in the measurement of ferritin in dried whole blood.” McDade 906 (citation omitted; emphasis added). Appeal 2019-004750 Application 13/772,796 14 In sum, given the disclosures in the McDade reference that a dried whole blood sample from a finger stick provides a sufficient amount of material for quantifying many analytes of interest by immunoassay, the unsupported statements in the McDade Declaration and Kelso Declaration do not persuade us that a skilled artisan lacked a reasonable expectation of success in using the McDade reference’s DBS sample as the whole blood sample in INSERM’s antibody-based AMH quantitation process. We are also unpersuaded that the Fleming reference demonstrates that skilled artisans would have considered the DBS samples described in the McDade to be an unsuitable sample for INSERM’s antibody-based AMH quantitation process. Fleming discloses a study in which it was determined that, if whole blood samples were stored at room temperature for too long before separation of serum from the samples, accuracy of an antibody-based assay of AMH in the serum was significantly affected. See Fleming 132 (“It is clear from these results that protracted storage of whole blood at room temperature profoundly influenced the AMH concentration measured in the subsequently separated serum.”). Appellant does not point to, nor do we discern, any specific discussion in Fleming as to whether the finger stick whole blood DBS samples taught in the McDade reference would be useful in an antibody-based AMH quantitation as taught in INSERM. Nor do we discern any disclosure in Fleming that specifically undermines the teachings in the McDade reference suggesting that DBS samples would reasonably be successful in INSERM’s AMH quantitation process. In sum, for the reasons discussed, Appellant does not persuade us that the Examiner erred in determining that a skilled artisan had a reasonable Appeal 2019-004750 Application 13/772,796 15 expectation of success in using the McDade reference’s DBS sample as the whole blood sample in INSERM’s antibody-based AMH quantitation process. Appellant also does not persuade us that the Examiner erred in determining that a skilled artisan had motivation for using the McDade reference’s DBS sample as the whole blood sample in INSERM’s antibody-based AMH quantitation process. As the Examiner points out, the McDade reference discloses that finger stick whole blood DBS samples have a number of advantages as compared to venipuncture. See McDade 907 (advantages of DBS as sample for analyte quantitation include “provid[ing] access to physiological information that would not otherwise be attainable in nonclinical settings;” “sample collection is relatively painless and noninvasive;” “unlike plasma or serum, DBS samples do not need to be centrifuged, separated, or immediately frozen following collection;” “DBS samples remain stable in laboratory freezers for long periods of time”). Given the advantages of finger stick whole blood DBS samples described in the McDade reference, we agree with the Examiner that a skilled artisan had good reason for obtaining a whole blood sample from a finger stick of a subject, and directly contacting that sample with labeled antibodies to quantify AMH, as taught in INSERM. Because a skilled artisan had a good reason for, and a reasonable expectation of success in, using the McDade reference’s whole blood finger stick DBS samples in INSERM’s labeled antibody-based AMH detection assays, we agree with the Examiner that the process recited in Appellant’s claim 56 would have been prima facie obvious. We also agree with the Appeal 2019-004750 Application 13/772,796 16 Examiner that Appellant has not advanced evidence of unexpected result sufficient to outweigh the evidence of prima facie obviousness. As to unexpected results, Appellant contends that, “[s]urprisingly, the present inventors observed that the correlation between concentrations of AMH in DBS samples and serum samples was linear across the range of detected levels as indicated in Figure 1, and the inventors calculated a Pearson correlation (R) of 0.968, which is very high.” Appeal Br. 17 (citing Kelso Decl. ¶ 7; emphasis omitted). As explained in the McDade reference, however, a skilled artisan would have expected a good correlation between analyte concentrations determined by finger stick DBS sample, as compared to assays of serum or plasma. See McDade 906 (“[I]nvestigators can expect performance that is comparable to that obtained with serum/plasma samples . . . .”); see also id. at 908 (“[T]he correlations between results derived from matched serum/plasma and DBS samples are linear and high for most analytes . . . .”). Moreover, as to the Kelso Declaration’s statement that the small amount of blood obtained from a finger stick (25 µL) makes assaying AMH concentration problematic and the results obtained unexpected (see Kelso Decl. ¶ 7), the McDade reference states that the DBS samples actually contain 50 µL of whole blood, twice the amount stated in the declaration. See McDade 905 (“When filled to its border, each circle will contain approximately 50 μL of whole blood.”); see also id. at 907 (“A typical drop of blood will contain approximately 50 μL of whole blood . . . .”). As to unexpected results, Appellant contends that the observed limit of detection in Appellant’s AMH immunoassay using a DBS sample was 0.052 ng/mL, which “is surprisingly low in comparison to other DBS Appeal 2019-004750 Application 13/772,796 17 immunoassays used for point of care detection. For example, the limit of detection for C-reactive protein in a DBS immunoassay typically is > 10-9 g/ml, which is 100-l000× higher than the limit of detection for the inventors’ AMH immunoassay.” Appeal Br. 17 (citing Kelso Decl. ¶ 9; emphasis omitted). Although neither Appellant nor the Kelso Declaration cites the specific portion of the Appellant’s disclosure that supports the statements regarding the allegedly unexpected lower detection limit, we note the Specification’s disclosure that “the minimum detectable dose of AMH was 0.052 ng/mL in this Example.” Spec. 22. That result, however, was obtained using a specific assay protocol using specific reagents (see id. at 18–20), whereas Appellant’s claim 56 does not recite any particular assay techniques or reagents, other than labeled anti-AMH antibodies. It is well settled that “[e]vidence of secondary considerations must be reasonably commensurate with the scope of the claims.” In re Kao, 639 F.3d 1057, 1068 (Fed. Cir. 2011). Moreover, to the extent Appellant and the Kelso Declaration advance the C-reactive protein detection limit as a basis for comparison with the results obtained in Appellant’s Specification, neither Appellant nor the Kelso Declaration explains specifically where a description of the C-reactive protein DBS immunoassay appears in the record. On this record, therefore, the Kelso Declaration’s statement as to typical results of a C-reactive protein DBS immunoassay, and the alleged unexpectedness of claim 56’s process in comparison thereto, lack clear objective evidentiary support. In sum, for the reasons discussed we agree with the Examiner that the process recited in Appellant’s claim 56 would have been prima facie Appeal 2019-004750 Application 13/772,796 18 obvious. For the reasons discussed, we also agree with the Examiner that Appellant has not advanced evidence of unexpected result sufficient to overcome the evidence of prima facie obviousness. We therefore affirm the Examiner’s rejection of claim 56 for obviousness over INSERM and McDade. Claims 58 and 59 fall with claim 56. 37 C.F.R. § 41.37(c)(1)(iv). OBVIOUSNESS—PLACE AND INSERM The Examiner’s Rejection In rejecting claims 40–46, 49, 50, and 54 over Place and INSERM, the Examiner cited Place as describing a process of using labeled antibodies to quantify AMH in a plasma, serum, or blood product sample. Ans. 8. The Examiner conceded that Place differs from the claims in that “Place does not specifically teach a whole blood sample; and fails to teach that the whole blood sample is from a finger stick.” Ans. 9. The Examiner cited INSERM as evidence that it would have been obvious to use a whole blood sample in Place’s process of quantifying AMH in a subject. Id. at 10. As to the recitation in independent claims 40 and 49 that the whole blood sample is obtained from a finger stick, the Examiner again determined that “[t]he process by which the whole blood sample is obtained does not clearly impart any structural different in this case to the resultant whole blood sample.” Ans. 9. Analysis For reasons similar to those discussed above in relation to the anticipation rejection of claim 40 over INSERM, we reverse this rejection. As discussed above, Appellant has advanced evidence, which the Examiner has not persuasively rebutted, that whole blood from a finger stick differs compositionally from other types of whole blood samples. Appeal 2019-004750 Application 13/772,796 19 Accordingly, on this record, neither Place nor INSERM describes, expressly or inherently, using labeled antibodies to quantify AMH in a whole blood sample from a finger stick, as required by claims 40 and 49. And the Examiner, in this rejection, has not advanced evidence why a skilled artisan would have considered it obvious to use whole blood from a finger stick in an antibody-based AMH assay. We therefore reverse the Examiner’s rejection of claims 40 and 49, and their dependent claims, for obviousness over Place and INSERM. OBVIOUSNESS— PLACE, INSERM, AND MCDADE The Examiner’s Rejection In rejecting claims 40–50 and 54–59 over Place, INSERM, and McDade, the Examiner again cited Place as describing a process of using labeled antibodies to quantify AMH in a plasma, serum, or blood product sample. Ans. 14. The Examiner again conceded that Place differs from the claims in that “Place does not specifically teach a whole blood sample; and fails to teach that the whole blood sample is from a finger stick.” Ans. 14. The Examiner again cited INSERM as evidence that it would have been obvious to use a whole blood sample in Place’s process of quantifying AMH in a subject. See id. at 10. The Examiner cited McDade as evidence that it would have been obvious to use whole blood from a finger stick as a sample when using labeled antibodies to quantify AMH in a subject, as taught in INSERM and Place. Ans. 15–16, 18. Appeal 2019-004750 Application 13/772,796 20 Analysis We select claim 56 as representative of the claims subject to this rejection. See 37 C.F.R. § 41.37(c)(1)(iv). Having carefully considered the arguments and evidence advanced by Appellant and the Examiner, Appellant does not persuade us that the preponderance of the evidence fails to support the Examiner’s conclusion of obviousness as to claim 56. In traversing this rejection, Appellant reiterates its arguments, addressed above, against the Examiner’s rejection of claim 56 over the combination of INSERM and McDade. See Appeal Br. 20–21. For the reasons discussed above, we are not persuaded that the Examiner erred in determining that the process of claim 56 would have been obvious in view of INSERM and McDade. Accordingly, we affirm the Examiner’s rejection of claim 56 over the combination of Place, INSERM, and McDade. Claims 40–50, 54, 55, and 57–59 fall with claim 56. 37 C.F.R. § 41.37(c)(1)(iv). OBVIOUSNESS— PLACE, INSERM, MCDADE, AND MOHAMMED Claims 51–53 depend directly or ultimately from claim 49, discussed above. See Appeal Br. 25–26. In rejecting claims 51–53, the Examiner cited Place, INSERM, and McDade for the teachings noted above, and cited Mohammed as evidence that the additional elements recited in claims 51–53 would have been obvious features of the process suggested by the remaining references. See Ans. 21–22. In traversing this rejection, Appellant does not identify, nor do we discern, specific error in the Examiner’s combination of Mohammed with the other references. Rather, Appellant reiterates its arguments, addressed Appeal 2019-004750 Application 13/772,796 21 above, against the Examiner’s rejection of claim 49 over Place, INSERM, and McDade. See Appeal Br. 21. For the reasons discussed above, we do not find those arguments persuasive. Accordingly, we also affirm the Examiner’s rejection of claims 51–53. CONCLUSION In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 40, 41, 46 102(b) INSERM 40, 41, 46 56, 58, 59 103(a) INSERM, McDade 56, 58, 59 40–46, 49, 50, 54 103(a) Place, INSERM 40–46, 49, 50, 54 40–50, 54–59 103(a) Place, INSERM, McDade 40–50, 54–59 51–53 103(a) Place, INSERM, McDade, Mohammed 51–53 Overall Outcome 40–59 TIME PERIOD No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED Copy with citationCopy as parenthetical citation